RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis - PubMed (original) (raw)
. 2015 Aug 10;28(2):253-69.
doi: 10.1016/j.ccell.2015.07.006.
Sabina Sangaletti 2, Francesca Maria Consonni [ 3](#full-view-affiliation-3 "Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro," Via Bovio 6, 28100 Novara, Italy."), Gabor Szebeni 1, Sara Morlacchi 1, Maria Grazia Totaro 1, Chiara Porta [ 3](#full-view-affiliation-3 "Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro," Via Bovio 6, 28100 Novara, Italy."), Achille Anselmo 1, Silvia Tartari 1, Andrea Doni 1, Francesco Zitelli [ 3](#full-view-affiliation-3 "Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro," Via Bovio 6, 28100 Novara, Italy."), Claudio Tripodo 4, Mario P Colombo 2, Antonio Sica [ 5](#full-view-affiliation-5 "Department of Inflammation and Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy; Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro," Via Bovio 6, 28100 Novara, Italy. Electronic address: antonio.sica@humanitasresearch.it.")
Affiliations
- PMID: 26267538
- DOI: 10.1016/j.ccell.2015.07.006
Free article
RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis
Laura Strauss et al. Cancer Cell. 2015.
Free article
Abstract
Cancer-driven granulo-monocytopoiesis stimulates expansion of tumor promoting myeloid populations, mostly myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). We identified subsets of MDSCs and TAMs based on the expression of retinoic-acid-related orphan receptor (RORC1/RORγ) in human and mouse tumor bearers. RORC1 orchestrates myelopoiesis by suppressing negative (Socs3 and Bcl3) and promoting positive (C/EBPβ) regulators of granulopoiesis, as well as the key transcriptional mediators of myeloid progenitor commitment and differentiation to the monocytic/macrophage lineage (IRF8 and PU.1). RORC1 supported tumor-promoting innate immunity by protecting MDSCs from apoptosis, mediating TAM differentiation and M2 polarization, and limiting tumor infiltration by mature neutrophils. Accordingly, ablation of RORC1 in the hematopoietic compartment prevented cancer-driven myelopoiesis, resulting in inhibition of tumor growth and metastasis.
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Comment in
- ROR1C Regulates Differentiation of Myeloid-Derived Suppressor Cells.
Gabrilovich D, Nefedova Y. Gabrilovich D, et al. Cancer Cell. 2015 Aug 10;28(2):147-9. doi: 10.1016/j.ccell.2015.07.007. Cancer Cell. 2015. PMID: 26267530 Free PMC article.
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